Polyphenols have been shown to inhibit the activity of these enzymes, thereby slowing down the rate of carbohydrate digestion and reducing the peak blood glucose response after a meal.

This effect has been observed with several polyphenol-rich foods, including green tea, grape seed extract, and resveratrol. In addition to their effects on carbohydrate digestion, polyphenols have also been shown to improve insulin sensitivity in various animal and human studies.

Insulin resistance is a condition in which cells become less responsive to the action of insulin, leading to elevated blood glucose levels. The exact mechanism by which polyphenols improve insulin sensitivity is not fully understood, but several possible explanations have been proposed.

One is that polyphenols may activate certain signaling pathways in cells that are involved in glucose uptake and metabolism. For example, studies have shown that catechins found in green tea can activate the AMPK pathway, which is a key regulator of energy metabolism in cells.

Activation of this pathway has been shown to improve insulin sensitivity and glucose uptake in various tissues, including muscle and fat cells. Another mechanism by which polyphenols may support insulin sensitivity is by promoting your anti-oxidant system which reduced oxidative stress.

These processes are known to impair insulin signaling and contribute to the development of insulin resistance. Polyphenols have been shown to reduce oxidative stress in various animal and human studies, which may explain their beneficial effects on insulin sensitivity and blood sugar control.

Finally, polyphenols may also have a direct effect on glucose uptake by cells. For example, quercetin, a flavonoid found in many fruits and vegetables, has been shown to increase glucose uptake in muscle cells, while catechins found in green tea have been shown to increase glucose uptake in fat cells.

These effects may contribute to the overall improvement in blood sugar control observed with polyphenol-rich diets. It is important to note that the effects of polyphenols on blood sugar metabolism are complex and may vary depending on the type and dose of polyphenol, as well as individual factors such as genetics and diet.

Additionally, most studies on polyphenols and blood sugar regulation have been conducted in animals and people.

However, there is a growing body of evidence to support the potential benefits of polyphenols for blood sugar metabolism and overall metabolic health. Some studies have also looked at the potential synergistic effects of combining different polyphenols, such as those found in a variety of plant-based foods.

For example, a study in rats found that a combination of resveratrol, quercetin, and catechins had a greater effect on improving insulin sensitivity than any of the polyphenols alone. Similarly, a study in humans found that a combination of green tea extract and grape seed extract improved insulin sensitivity and glucose uptake in muscle tissue compared to a placebo.

In conclusion, polyphenols are a class of bioactive compounds found in a variety of plant-based foods that have the potential to improve blood sugar metabolism and prevent the development of metabolic misfire. While more research is needed to fully understand the potential benefits of polyphenols for metabolic health, the available evidence suggests that including a variety of polyphenol-rich foods in the diet may be a simple and effective way to support overall health and well-being.

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Therefore, subscribing to our newsletter is a great way to get access to exclusive information as well. Sign up now and don't miss out on any of the exciting new developments at CELLg8®! Popular Keywords. Load More Results. Facebook-f Twitter Instagram Youtube Linkedin. The bioavailability and metabolism of polyphenols should be considered in future studies.

Many available studies have shown an effect after oral administration in animal models, but clinical studies have provided variable results, which could be due to dose, methodology or differences in bioavailability or metabolism. Some polyphenols are bioavailable in their native form. ECGC is found in plasma in free form following oral administration, albeit at low concentrations Andreu-Fernandez et al.

Resveratrol can be absorbed in its native state but can also undergo considerable microbial metabolism before absorption Bode et al. However, some polyphenols are largely metabolized before absorption. Rutin is metabolized by microbiota before the metabolites are absorbed in both humans and rodents Baba et al.

There is significant interspecies variation in the metabolism of xenobiotics. For example, resveratrol and dihydroresveratrol in human subjects after oral administration have been observed at higher plasma levels than those obtained in mice given considerably higher doses Timmers et al.

Furthermore, interindividual differences in the metabolism and absorption of compounds may underlie clinical variability. The level of bioavailability of resveratrol between individuals is inconsistent. Microbial metabolism between individuals can vary greatly, which may explain the conflicting results from human trials Bode et al.

The bioactivity of most metabolites of polyphenolic compounds is poorly understood. The plasma level of free, unconjugated quercetin following rutin supplementation is reported to be low Erlund et al.

Despite this, an antidiabetic effect has been reported following oral rutin administration in vivo , raising the question of whether one or more metabolites are responsible Aitken et al. So far, there has been little published research on the activities of metabolites and their link to the clinical efficacy of the parent compound.

Bioavailability and metabolism should be considered in the design of future intervention studies Manach et al. An avenue for further research may be to design drugs based on polyphenolic structures that may be more stable or targeted in the body, or with novel delivery systems, to improve absorption and efficacy.

The inhibitory effects of polyphenols on hA aggregation are often studied in vitro in aqueous solutions; however, this does not accurately recapitulate the lipid membrane environment in which hA aggregates physiologically.

Studies utilizing a variety of membrane-mimetic model systems have demonstrated that lipid membranes containing an anionic charge accelerate fibril formation Knight et al. However, few studies have reported on the ability of polyphenols to inhibit hA aggregation in such an environment, with results only for EGCG and resveratrol reported to our knowledge.

By contrast, resveratrol inhibited hA aggregation even in the presence of lipids Evers et al. Further investigation into whether other polyphenols retain their inhibitory effect on amyloid formation in a lipid membrane environment would be valuable.

This opens the possibility that polyphenols, especially with their pleiotropic effects, may be an effective treatment for several diseases.

The antioxidant and anti-inflammatory activities of polyphenols have non-disease specific, beneficial effects that may be especially useful for those diseases with a complicated and varied etiology like T2DM. Additionally, with their well-tolerated safety profile there is the possibility for use of polyphenolic compounds as a preventative as well as therapeutic treatment.

Future studies should carefully consider the methodologies they use. As discussed, ThT fluorescence should not be used as the sole method to measure inhibition of hA aggregation by compounds due to the possibility of competitive binding Daval et al.

Circular dichroism, atomic force microscopy or other methods should be utilized to verify results. High resolution nuclear magnetic resonance or mass spectrometry techniques could be used to probe the specific interaction of compounds with hA, which could provide vital insights into the binding mechanism and facilitate rational drug design based on polyphenolic compounds.

For in vivo studies, the appropriateness of the animal model used must also be considered, as many models recapitulate part of but not the entirety of T2DM. Many commonly used models, such as STZ or alloxan-induced diabetic animals, are more reminiscent of T1DM than T2DM. Few studies utilize transgenic mice that express the human variant of amylin which forms amyloid Aitken et al.

Similarly, the use of cell lines that overexpress hA in in vitro studies, rather than applying exogenous hA to cells, may be more physiologically relevant.

For decades, T2DM was considered as predominantly a disease caused by insulin resistance and therapies focused on lowering blood glucose levels. However, in recent years there has been a paradigm shift, from a glucose-centric to a β-cell-centric view of T2DM Saisho, This evolution recognizes that T2DM occurs only when β-cell function has failed.

The etiology underlying this process is unclear; however, evidence suggests that cytotoxic hA oligomers, oxidative stress, inflammation, ER stress and mitochondrial dysfunction all play their part, even if a single causative mechanism if there is indeed one is yet to be determined.

Therefore, agents that target multiple pathways may lead to better therapeutic outcomes. In this regard, polyphenols are promising candidates with their ability to inhibit amyloid formation Porat et al. As hA oligomers have been shown to contribute to oxidative stress Zraika et al.

Additionally, polyphenols have more direct effects on reducing oxidative stress and inflammation, as well as modulating other cellular pathways with beneficial metabolic effects.

Thus, polyphenols may have beneficial effects on both β-cell survival and whole-body insulin sensitivity. Both scientists and the public have shown strong interest in polyphenols, their potential health benefits, and their use as treatments for a multitude of diseases, especially surrounding EGCG, resveratrol, and curcumin.

However, hopes for a new effective therapeutic treatment based on the findings summarized here have yet to come to fruition.

Clinical trials have shown some encouraging but controversial results. The greatest challenge appears to be achieving a consistent therapeutic effect. The current impasse may be due to incomplete understanding of the molecular basis of polyphenol action, alongside the complexity of multifactorial diseases such as T2DM.

Further research could usefully focus on the following: 1 the bioavailability of compounds in humans and establishing a therapeutic dose range; 2 the identity and activity of metabolites; 3 consideration of methodology for in vitro studies and in vivo trials and ensuring that clinical trials examine appropriate parameters; 4 design of compounds or delivery systems with greater stability and improved and reproducible efficacy.

Natural polyphenols remain an active area of research for many diseases Khursheed et al. Improved compounds and robust study designs will enable greater understanding of how to utilize these interesting, multifunctional compounds.

TN wrote the article, GC revised the article and contributed discussions on the content. Our research programme has been funded by the Ministry for Business, Innovation and Employment, New Zealand Government.

Funding identification: CONTENDRP-UOA UOAX for research programme entitled Optimized disease-modifying therapy for type-2 diabetes. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Int Food Res J ; 22 1 : Shahidi F, Ambigaipalan P. Another challenge is that polyphenol levels can vary considerably. For instance, organic fruits sometimes have higher levels of polyphenols than nonorganic fruits.

Other factors, like rainfall, sun exposure , and how food is stored and prepared can also alter a food's polyphenol levels. Above, we outlined epidemiological studies that included large numbers of people.

These are important in helping scientists spot patterns and associations. Then, scientists run smaller, more tightly controlled studies to understand whether those associations are causal. These are clinical trials. The researchers recruited 86 participants with overweight or obesity and assigned them to four groups.

Each followed a different diet, some of which were rich in polyphenols. At the beginning and end of the study, the scientists gave the participants a test meal and measured their blood sugar responses. At the end of the study, participants with the high-polyphenol diets had significantly reduced blood sugar responses.

The scientists recruited 34 people with prediabetes. People with prediabetes have higher than usual blood sugar levels, but these are still too low for a diagnosis of type 2 diabetes. Half the participants took an acacia polyphenol supplement each day for 8 weeks, and the other half took a placebo.

The team found that participants taking the polyphenol supplement had significantly reduced blood sugar responses to a meal at the end of the study, compared with the beginning.

This wasn't true for the people who took the placebo. By now, several clinical trials have measured the positive effects of polyphenols on blood sugar control. So, the next question is …. If these wonderful plant compounds really do influence blood sugar control and protect against type 2 diabetes, how are they doing it?

Evidence suggests that polyphenols probably work their magic via a number of routes. Enzymes need to snip them into simple sugars, like glucose, before they can enter your blood. Polyphenols slow this process by inhibiting some of the carb-snipping enzymes. Once carbs have been chopped up into glucose, they move through your gut lining using glucose transporters.

Polyphenols may also interact with these transporters, slowing the movement of glucose from your gut to your blood.

So, polyphenols seem to hinder the breakdown of larger carb molecules and slow their passage into your blood. Evidence from lab and animal studies suggests that polyphenols can help your body remove glucose from your blood more quickly. It might do this by increasing your insulin sensitivity, which means that glucose is more efficiently shunted out of your blood.

Also, lab studies suggest that polyphenols can increase the number or sensitivity of glucose transporters on muscles. This means that glucose is moved from your blood into your muscles more efficiently.

Instead, they reach your large intestine, where they feed your gut bacteria and keep them happy. Some evidence suggests that polyphenols might increase numbers of Bifidobacteria in your gut. And increased numbers of Bifidobacteria seem to be associated with better blood sugar control.

The full story of how gut bacteria are involved is yet to be told. Scientists are still digging into the links between polyphenols, blood sugar control, and type 2 diabetes.

But evidence is mounting that these plant compounds can positively influence your blood sugar control and may reduce your type 2 diabetes risk. As researchers continue to uncover the link between these plant chemicals and the risk of developing type 2 diabetes, upping your polyphenol intake is a safe bet.

Aside from blood sugar control, polyphenols may also protect heart, gut, and skin health. Scientists are still unraveling the roles that polyphenols play in our health. But because plant foods that are good for your health contain high levels of polyphenols , increasing your intake of these plants will likely benefit you.

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Nutrients, 7 4 : p. Related Articles. The Superior Benefits of Magnesium and the Whole Food Matrix Magnesium Mg is an essential nutrient, participating in a variety of body functions and supporting multiple body systems.

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